1. Field of the Invention
The present invention relates to a novel percutaneous absorption promoter. More particularly, the present invention relates to a percutaneous absorption promoter, having excellent ability of promoting percutaneous absorption of a pharmacologically active substance and excellent safety simultaneously, capable of delivering the desired pharmacologically active substance rapidly to the location of treatment or to all parts of the body through the circulating system and effective for curing various kinds of disease. The present invention relates also to a novel tape plaster comprising the percutaneous absorption promoter therefore and a novel method of promoting percutaneous absorption by utilizing it.
2. Description of the Prior Art
During the recent progress of medical treatment, transdermal therapeutic systems therefore (TTS) have been developed to absorb percutaneously and deliver desired pharmacologically active substances to all parts of the body and thus to maintain the curing effect for a prolonged time. For example, transdermal therapeutic systems utilizing nitroglycerol or isosorbide dinitrate for curing angina pectoris, those containing clonidine for curing hypertonia and those containing estradiol for curing climacteric difficulties have actually been utilized.
However, even though these transdermal therapeutic systems show many advantages such as evasion of metabolism of the pharmacologically active substances at intestine and liver, reduction of side reactions and increased retention of the pharmacological effect, they have a problem that, because skin essentially has the barrier function against invasion of foreign substances, only limited kinds of pharmacologically active substances can attain the concentration of the substances in blood high enough to show the pharmacological effect and the pharmacologically active substances which can be utilized for the transdermal therapeutic systems are naturally very limited.
Various methods have been tried to improve the percutaneous absorption of pharmacologically active substances. For example, pharmacologically active substances were modified to form prodrugs and complexes. Ionic pharmacologically active substances were utilized with use of iontophoresis. These methods have a problem that the actual administration requires detailed studies on the individual pharmacologically active substance and a long period of time and a large amount of investment are inevitably required. On the other hand, percutaneous absorption promoters which increase percutaneous absorption of pharmacologically active substances by decreasing the barrier property of skin have been actively developed. It is expected by using these percutaneous absorption promoters that various kinds of pharmacologically active substances can be utilized without much limitations.
As the percutaneous absorption promoters, the following compounds, for example, have been utilized: polar solvents, such as dimethylsulfoxide, decylmethylsulfoxide, dimethylformamide and dimethylacetamide; cycloalkanes, such as azacycloheptan-2-one and 1-dodecylazacyloheptan-2-one; esters of carboxylic acids and alcohols, such as isopropyl myristate and isopropyl palmitate; glycols; surface active agents, such as sodium laurylsulfate and sodium dodecylsulfate; and derivatives of fatty acids, pyroglutamic acid and urea which are natural moisturing agents of skin. These absorption promoters have problems that they do not always satisfy both the promotion of the percutaneous absorption and safety, such as safety concerns from toxicity and irritation, and that a long time is required to exhibit the pharmacological activity because of a long lag time in the percutaneous absorption of the pharmacologically active substances.